The reticuloendothelial system (RES) is an important host defense system during circulatory shock. This is based on numerous studies which have shown a positive correlation between RES function during shock and host survival. Recent work has shown that circulating activity of an opsonic alpha-2-glycoprotein modulates RES function under several conditions associated with depressed hepatic phagocytosis. The proposed study was designed to assess the possible involvement of opsonin depletion in the RES depression during hemorrhagic shock. Results obtained to date clearly show that RES clearance capacity is markedly depressed during experimental hemorrhagic shock and that this is associated with a large depletion of circulating opsonic activity. Studies presently underway will evaluate the contribution of altered splanchnic blood flow to the observed depression of RES function. Future studies will examine the effect of opsonin depletion prior to shock and its effect on RES function during shock and shock survival. Additionally, the present capability of isolating purified opsonic protein provides the means to directly evaluate the role of humoral opsonic factors in the regulation of RES function. The effect of "opsonin therapy" on circulatory shock survival will reveal the role of opsonic protein depletion in the pathogenesis of irreversible shock.